The epidermis is a stratified epithelium consisting of numerous cell layers. The principal cell type of the epidermis is the keratinocyte. Keratinocytes are responsible for the resistance of the skin to physical and chemical injury and for its impermeability to water. These functions are carried out primarily by the outermost layer of keratinocytes, termed xe2x80x9ccorneocytes,xe2x80x9d which have undergone programmed cell death. Corneocytes consist of a skeletal framework of keratin filaments surrounded by a special envelope that is found in no other cells within the body. This envelope consists of proteins (xe2x80x9ccorneocyte proteinsxe2x80x9d) stabilized by inter-molecular isopeptide bonds (Rice and Green (1977), Cell, 11:417-422). The bonds are introduced by an enzyme, calcium-activated keratinocyte transglutaminase (Rice and Green (1979), Cell, 18:681-694). As skin ages, the epidermis atrophies with accompanying diminution of its physical resistance.
The basal layer of the epidermis contains proliferating keratinocytes. When keratinocytes leave the basal layer, they begin to undergo terminal differentiation. When they reach the granular layer, the concentration of calcium ions inside the keratinocytes rises, resulting in activation of transglutaminase. The envelope precursor proteins, which at this stage are located just beneath the plasma membrane, are crosslinked by transglutaminase (Rice and Green (1979), ibid.; Greenberg et al. (1991) FASEB, 5:3071-3077) and the resulting envelope becomes thoroughly insoluble, even in the presence of detergents and reducing agents (Green (1977), Cell, 11:405-416; Hohl (1990), Dermatologica, 180:201-211). This envelope is the most resistant structure of the skin since keratin filaments, even though they are stabilized by disulfide bonds, can be dissolved by a combination of detergent and reducing agent. Transglutaminase and its crosslinked products are also present in hair and nails (Rice et al., Keratinocyte Handbook, (in press)).
The invention comprises a composition suitable for topical application to mammalian skin, hair and/or nails comprising a corneocyte protein, or polypeptide fragment thereof. The proteins or polypeptides are dispersed in a cosmetically acceptable vehicle which is designed to permit effective application of the proteins or polypeptides to the skin, hair or nails. A method for forming a protective layer on mammalian skin, hair or nails by applying a topical cosmetic composition containing an effective amount of the proteins or polypeptides also is the subject of the present invention.
The composition alternatively may comprise a crosslinking agent which is specific for corneocyte proteins, i.e., which forms crosslinks or induces crosslinking between corneocyte proteins already present in the stratum corneum. The crosslinking agent may be a chemical agent which reacts with two or more functional groups present in amino acid side chains of the proteins thereby forming crosslinks between the amino acids of different proteins. Chemical crosslinkers, such as glutaraldehyde, typically are themselves incorporated into the crosslink. Alternatively, the crosslinking agent may be an enzyme, such as transglutaminase, which induces formation of crosslinks between glutamine and lysine residues of adjacent polypeptides.
Corneocyte proteins which are preferred for use in the present composition and method include involucrin, loricrin, cornifin, trichohyalin, sciellin, profilaggrin and keratolinin and/or polypeptide fragments of these proteins. The proteins or polypeptides may be natural-sourced or recombinant. The proteins or polypeptides may be crosslinked, if desired, using a chemical crosslinker or an enzyme which forms bonds between adjacent polypeptides. Optionally, the proteins or polypeptides may be modified, for example, by chemically derivatizing or substituting one or more of the amino acids in the protein or polypeptide chain. Such modifications can be designed to impart specific properties to the protein or polypeptide for a selected application.
In a preferred embodiment, a protective layer is formed on skin, hair or nails by applying thereto a composition containing one or more corneocyte proteins or polypeptides. The proteins or polypeptides may be crosslinked to form the protective layer. For this purpose, a crosslinking agent capable of inducing formation of isopeptide bonds between molecules of the protein or polypeptide preferably is included in the composition. In another embodiment, a composition comprising only the crosslinking agent is applied, thereby inducing crosslinking of proteins already present in the skin, hair or nails. The presence of the crosslinking agent induces formation of a crosslinked protein network analogous to the corneocyte envelope which occurs naturally in skin. The protein network forms a protective layer on the skin, hair or nails which can help protect the skin, hair or nails from physical, environmental or chemical injury. Specific protectants, such as moisturizers or sunscreens, optionally may be included in the cosmetic composition.